RNA origami as a vaccine assembly platform to promote CD8 T Cell mediated anti-tumor immunity

Abstract CD8 T cell mediated immunity is critical for controlling tumor growth. However, constructing synthetic vaccines that can effectively induce this arm of the immunity has been challenging. With the advancement of nanotechnologies, various nanostructures have been explored to link antigens and adjuvants together for increased stability, lymph node delivery, cellular uptake, and activation of innate immunity, all of which may help elicit potent T cell responses against tumors. Here, we explored a self-assembling RNA origami (RNA-OG) nanostructure as a vaccine platform to assemble tumor antigens. In addition to acting as an antigen carrier, RNA-OG is an intrinsic TLR3 agonist and therefore functions as a potent adjuvant. Thus, these RNA-OG-antigen vaccines offer simultaneous delivery of antigens and adjuvants for better initiation of T-cell mediated immunity. We demonstrated enhanced antigen cross-presentation of RNA-OG-linked antigens by dendritic cells and subsequent induction of antigen-specific CD8-T cell responses. Using B16-OVA (ovalalbumin) murine melanoma tumor model, RNA-OG-OVA vaccines induced an anti-tumor immune response that contributed to long-term tumor immunity and increased survival of the animals. Overall, our data demonstrates that RNA-OG can function as a potent anti-tumor vaccine platform.